Ocular infections such as bacterial keratitis are serious clinical problems. Bacterial keratitis, for example, is a component of many ocular infections, especially among those who have sustained penetrating corneal injuries, used extended-wear contact lenses, undergone incisional refractive surgery, or are immunocompromised. Bacterial keratitis is an important cause of visual morbidity. Contact lens wearers are most at risk. More recently, the use of refractive correction in the form of incisional and laser surgery has emerged as a new cause of bacterial keratitis (1-4). Loss of vision and permanent scarring are commonly due to toxic bacterial products and the host inflammatory response to wounding and infection. Common causative organisms are the Gram positive bacteria Staphylococcus aureus and the Gram negative bacterium Pseudomonas aeruginosa (5-7). The bacterial products and toxins and host inflammatory reaction stimulated in response to wounding and infection often leads to extensive tissue damage with permanent scarring and irreversible loss of vision (1).
Current treatments include the use of broad spectrum antibiotics. Topical antibiotic drops are the preferred treatment for corneal and conjunctival infections. Intravitreal antibiotics are preferred for endophthalmitis and parenteral antibiotics are recommended for deep infections.
The diagnosis and treatment of bacterial keratitis remains controversial. A combination of a fortified topical cephalosporin and a fortified topical aminoglycoside were once the first line of therapy. However, recently this therapy has been replaced by fluoroquinolones such as ciprofloxacin and oflaxacin for topical ophthalmic therapy. However, the emergence of methicillin-resistant organisms has reduced the effectiveness of these antibiotics. Thus the choice of initial empirical therapy is controversial. Clearly, there is a crisis situation developing with organisms that cause ocular infections which are resistant to antibiotics.
Because early treatment of the infection is important to prevent loss of vision, treatment is generally started before the specific identity of the causative organism and its sensitivity are known. Therefore, a broad spectrum antibiotic is generally used initially. Once the culture results are known the treatment is best modified to a single drug to cover the infectious organisms. It is important that the specific antibiotic have as narrow a spectrum as possible, since broad spectrum agents could unnecessarily alter the normal flora allowing super infection from resistant or nonsusceptible organisms.
Steroid treatment has also been used in conjunction with antibiotics in the hope that it will limit the inflammatory process of the host, however this course of treatment requires careful monitoring.
Almost all topical ophthalmic antibiotics can cause local irritation and allergic reactions. Treatment for severe bacterial keratitis (bacterial corneal ulcer), regardless of the identity of the antimicrobial agent used, typically consists of instillation of drug every 15-30 minutes around the clock for the first 2-3 days. The dosing interval is then gradually increased to every four hours and continued for an additional 14 days. Topical drops are preferred for corneal and conjunctival infections. The agent should be bactericidal rather than bacteriostatic.
The cornea is normally considered a “privileged” site because of its avascularity and lack of lymphatic vessels (8-10). Antigens, cytokines, inflammatory mediators and leukocytes that enter into the cornea must do so from the limbic and/or ciliary body vessels. Inflammatory cytokines and/or chemotactic gradients that are elicited locally by corneal cells could therefore profoundly affect the emigration of leukocytes from the limbic and ciliary circulation to the cornea.
Extravasation of leukocytes from the circulation into tissue sites is an integral feature of the host response to injury and inflammation. By virtue of their ability to engulf and destroy bacteria, eliminate toxins and secrete numerous soluble mediators, leukocytes are capable of restricting and limiting the spread of infection. Neutrophils (PMNs) are the predominant cell type in the early phases of inflammation and are soon followed by a second wave of cells composed mainly of monocytes and lymphocytes. Irreversible damage to the eye can occur in cases of fulminant inflammation. Clearly the desirable outcome is one in which the immune system can control the infection resulting in re-epithelialization and healing with minimum damage to vision.
The identification of a corneal derived chemotaxin or inflammatory mediator could be of extreme importance in our understanding of the mechanisms that regulate leukocyte migration, epithelial-leukocyte interaction, corneal inflammation and healing and in identifying methods of treatment of corneal damage related to infection, inflammation and physical wounding.